The overall aim of this project is to identify the gene or genes responsible for limb malformations in humans. The Human Genetic Studies Core and Cell immortalization Laboratory of the CRC would be utilized for the production of immortalized cell lines from subjects as they are identified. The availability of lymphoblast cells will facilitate delineation of the specific genetic defect. Lymphocytes will be immortalized with EBV to provide a renewable supply of cells and DNA for analysis.